1,2-Dichloroethane → 5-(trifluoromethyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione hydrochloride

HRID 12756Notes

Reaction equation

HRID 12756 reaction equation
[F:1][C:2]([F:16])([F:15])[C:3]1[C:4](=[O:14])[NH:5][C:6](=[O:13])[N:7]([CH2:9][CH2:10][CH:11]=O)[CH:8]=1.[F:17][C:18]([F:32])([F:31])[C:19]1[CH:24]=[CH:23][C:22]([C@:25]23[CH2:30][C@H:29]2[CH2:28][NH:27][CH2:26]3)=[CH:21][CH:20]=1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[Cl:51]CCCl>C(OCC)(=O)C>[ClH:51].[F:1][C:2]([F:16])([F:15])[C:3]1[C:4](=[O:14])[NH:5][C:6](=[O:13])[N:7]([CH2:9][CH2:10][CH2:11][N:27]2[CH2:28][C@H:29]3[C@:25]([C:22]4[CH:21]=[CH:20][C:19]([C:18]([F:17])([F:32])[F:31])=[CH:24][CH:23]=4)([CH2:30]3)[CH2:26]2)[CH:8]=1

Participants

7

Reactant 5

HCID 111,2-Dichloroethane2×HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 589941853-(5-Trifluoromethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionaldehydeHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

Product 1

HCID 866159515-(trifluoromethyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione hydrochlorideYield 51%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(5-trifluoromethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionaldehyde (Prep21, 0.05 g, 0.21 mmol) in DCE (1 mL), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 0.08 g, 0.35 mmol) in DCE (1 mL), AcOH (20 μl, 0.36 mmol) and NaBH(AcO)3 (0.09 g, 0.42) were added and the mixture was stirred at room temperature overnight. Ethyl acetate was added and the solution washed with aqueous saturated NaHCO3. The organic phase was dried (Na2SO4) and evaporated. The crude was purified by flash chromatography with DCM-MeOH—NH4OH (97-3-1) to give the title compound (0.04 mg, 51% yield) as a free base.

Workup

  1. washthe solution washed with aqueous saturated NaHCO3
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. customevaporated
  4. customThe crude was purified by flash chromatography with DCM-MeOH—NH4OH (97-3-1)

Sources & evidence

ORD record
ord-97bae88de57f4bc1aa41a5f634eb98c9
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Reaction notes

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